First Observations on Reversible Binding of Steroids to Proteins

Abstract

As early as 1913, the pharmacologist Ernst Oppenheimer, at the age of 25, published studies on the behavior of cardiac-active compounds of the digitalis series (1913). He observed a decrease of toxicity towards the isolated frog heart when serum was added to the drug solutions. After testing several possible interpretations experimentally, Oppenheimer suggested as the most likely explanation for the reduced toxicity a binding (“adsorption”) of the cardiac-active steroid to the colloidal components of the serum. This binding was assumed to be easily dissociable so that the active compound is taken up by the heart cells which themselves have similar adsorption affinity; the result is a binding equilibrium (“Adsorptionsgleichgewicht”) in which the steroid is distributed between the serum colloids and the heart cells. This interpretation clearly is a precursor of the concepts of Storm van Leeuwen; it was ignored or forgotten by the investigators of the time. Subsequent research, however, gives ample evidence of Ernst Oppenheimer’s remarkable foresight.